Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, and ADMET Studies of 4-Thiazolidinone Derivatives

The design and development of new small-molecule glycation inhibitors are essential for preventing various chronic diseases, including diabetes mellitus, immunoinflammation, cardiovascular, and neurodegenerative diseases. 4-Thiazolidinone or thiazolidine-4-one is a well-known heterocyclic compound with the potential to inhibit the formation of advanced glycation end products. In the present work, we report the synthesis and characterization of four new 5-arylidene 3-cyclopropyl-2-(phenylimino)thiazolidin-4-one (1–4) compounds and their human serum albumin glycation inhibitory activity. One of the compounds 5-(2H-1,3-benzodioxol-5-ylmethylidene)-3-cyclopropyl-2-(phenylimino)-1,3-thiazolidin-4-one (3) showed potent inhibition in the synthesis of initial, intermediary, and final products of glycation reactions. Besides, conformational changes in the α-helix and β-sheet (due to hyperglycemia) were also found to be reversed upon the addition of (3). Experimental findings were complemented by computational [molecular docking, ADME/Tox, and density functional theory (DFT)] studies. The docking scores of the compounds were in order 1 \u3e 3 \u3e 2 \u3e 4, indicating the importance of the polar group at the 5-arylidene moiety. The results of ADME/Tox and DFT calculations revealed the safe nature of the compounds with high drug-likeness and stability. Overall, we speculate that the results of this study could provide valuable insights into the biological activity of 4-thiazolidinones

Levels of State and Trait Anxiety in Patients Referred to Ophthalmology by Primary Care Clinicians: A Cross Sectional Study

Purpose There is a high level of over-referral from primary eye care leading to significant numbers of people without ocular pathology (false positives) being referred to secondary eye care. The present study used a psychometric instrument to determine whether there is a psychological burden on patients due to referral to secondary eye care, and used Rasch analysis to convert the data from an ordinal to an interval scale. Design Cross sectional study. Participants and Controls 322 participants and 80 control participants. Methods State (i.e. current) and trait (i.e. propensity to) anxiety were measured in a group of patients referred to a hospital eye department in the UK and in a control group who have had a sight test but were not referred. Response category analysis plus infit and outfit Rasch statistics and person separation indices were used to determine the usefulness of individual items and the response categories. Principal components analysis was used to determine dimensionality. Main Outcome Measure Levels of state and trait anxiety measured using the State-Trait Anxiety Inventory. Results State anxiety scores were significantly higher in the patients referred to secondary eye care than the controls (p0.1). Rasch analysis highlighted that the questionnaire results needed to be split into “anxiety-absent” and “anxiety-present” items for both state and trait anxiety, but both subscales showed the same profile of results between patients and controls. Conclusions State anxiety was shown to be higher in patients referred to secondary eye care than the controls, and at similar levels to people with moderate to high perceived susceptibility to breast cancer. This suggests that referral from primary to secondary eye care can result in a significant psychological burden on some patients

Flexible visiting positively impacted on patients, families and staff in an Australian Intensive Care Unit: A before-after mixed method study

Background The admission of a relative to intensive care is stressful for families. To help them support the patient, families need assurance, information and an ability to be near their sick relative. Flexible visiting enables patient access but the impact of this on patients, families and staff is not clear. Objective To assess the impact of flexible visiting from the perspective of patients, families, and Intensive Care Unit (ICU) staff. Methods A before-after mixed method study was used with interviews, focus groups and surveys. Patients were interviewed, family members completed the Family Satisfaction in ICU survey and ICU staff completed a survey and participated in focus groups following the introduction of 21 h per day visiting in a tertiary ICU. The study was conducted within a philosophy of family-centred care. Results All interviewed patients (n = 12) positively evaluated the concept of extended visiting hours. Family members’ (n = 181) overall ‘satisfaction with care’ did not change; however 85% were ‘very satisfied’ with increased visiting flexibility. Seventy-six percent of family visits continued to occur within the previous visiting hours (11 am–8 pm) with the remaining 24% taking place during the newly available visiting hours. Families recognised the priority of patient care with their personal needs being secondary. Three-quarters of ICU staff were ‘satisfied’ with flexible visiting and suggested any barriers could be overcome by role modelling family inclusion. Conclusion Patients, families and ICU staff positively evaluated flexible visiting hours in this ICU. Although only a minority of families took advantage of the increased hours they indicated appreciation for the additional opportunities. Junior staff may benefit from peer-support to develop family inclusion skills. More flexible visiting times can be incorporated into usual ICU practice in a manner that is viewed positively by all stakeholders

Comparison of Decellularization Protocols to Generate Peripheral Nerve Grafts: A Study on Rat Sciatic Nerves

In critical nerve gap repair, decellularized nerve allografts are considered a promising tissue engineering strategy that can provide superior regeneration results compared to nerve conduits. Decellularized nerves offer a well-conserved extracellular matrix component that has proven to play an important role in supporting axonal guiding and peripheral nerve regeneration. Up to now, the known decellularized techniques are time and effort consuming. The present study, performed on rat sciatic nerves, aims at investigating a novel nerve decellularization protocol able to combine an effective decellularization in short time with a good preservation of the extracellular matrix component. To do this, a decellularization protocol proven to be efficient for tendons (DN-P1) was compared with a decellularization protocol specifically developed for nerves (DN-P2). The outcomes of both the decellularization protocols were assessed by a series of in vitro evaluations, including qualitative and quantitative histological and immunohistochemical analyses, DNA quantification, SEM and TEM ultrastructural analyses, mechanical testing, and viability assay. The overall results showed that DN-P1 could provide promising results if tested in vivo, as the in vitro characterization demonstrated that DN-P1 conserved a better ultrastructure and ECM components compared to DN-P2. Most importantly, DN-P1 was shown to be highly biocompatible, supporting a greater number of viable metabolically active cells.Ministry of Health, ItalyFondazione Cassa di Risparmio di Torino (Turin, Italy) 2017.AI190.U219 RF: 2016.2388Spanish "Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) FIS PI17-0393 FIS PI20-0318Fondo Europeo de Desarrollo Regional ERDF-FEDER European UnionPlan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020), Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, España P18-RT-5059Programa Operativo FEDER Andalucía 2014-2020, Universidad de Granada, Junta de Andalucía, España A-CTS-498-UGR18ERDF-FEDER, the European Unio

Annalen der Physik ; t. XLIII, nos 3 et 4; 1914

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The duo “pascaline and e-pascaline”: an example of using material and digital artefacts at primary school.

International audienceThe paper presents the design and the analysis of teaching experiments at primary school concerning the introduction and use of a “duo of artefacts”, constituted by the pascaline i.e., the arithmetical machine Zero+1 and its digital version e-pascaline. The idea of ‘duo of artefacts’ represents the innovative component of this research work, because the e-pascaline is constructed in a complementary way with respect to the pascaline. The duo of artefacts is proposed to support student’s conceptualization processes of numbers as sign of a quantity, number sequences and recursive addition. Computation and manipulation of base ten notation are two processes that students often consider separately. This duo enables the design of situations that required those two processes to be connected and to consider their effect on each other. With duo of artefacts, technology allows the development of learning environments in which it is possible to study the articulation between material and virtual manipulatives for mathematical conceptualization